Expression Signatures of Metastatic Capacity in a Genetic Mouse Model of Lung Adenocarcinoma

Abstract

Non-small cell lung cancer (NSCLC) is the foremost cause of cancer-related death in Western countries, which is due partly to the propensity of NSCLC cells to metastasize. The biologic basis for NSCLC metastasis is not well understood. Here we addressed this deficiency by transcriptionally profiling tumors from a genetic mouse model of human lung adenocarcinoma that develops metastatic disease owing to the expression of K-ras^G12D and p53^R172H. We identified 2,209 genes that were differentially expressed in distant metastases relative to matched lung tumors. Mining of publicly available data bases revealed this expression signature in a subset of NSCLC patients who had a poorer prognosis than those without the signature. These findings provide evidence that K-ras^G12D; p53^R172H mice recapitulate features of human NSCLC metastasis and will provide a useful platform on which to study the biologic basis for lung adenocarcinoma metastasis and its prevention by novel agents.